CASE REPORT
Year : 2014 | Volume
: 25 | Issue : 2 | Page : 402--407
Crescentic glomerulonephritis in non-asthmatic Churg-Strauss syndrome
Anupma Kaul1, Raj Kumar Sharma1, Krishna Swamy Jaisuresh1, Vinita Agrawal2,
1 Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Correspondence Address:
Anupma Kaul
Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh
India
Abstract
A 58-year-old male presented with sensory motor polyneuropathy and rapidly progressive renal failure. Investigations revealed marked peripheral eosinophilia and elevated perinuclear antineutrophil cytoplasmic antibody titers. Renal biopsy showed pauci-immune crescentic glomerulonephritis with interstitial eosinophil infiltrates. He had no history of asthma. Computed tomography of the chest and X-ray of the paranasal sinuses were normal. On Day 1, the patient developed ileal perforation. Resected ileal segments showed small vessel vasculitis with extravascular eosinophils. A diagnosis of non-asthmatic variant of Churg-Strauss syndrome was made. Renal recovery was achieved in 12 weeks with a combination therapy of corticosteroid and cyclophosphamide. The patient has been relapse-free for 12 months on oral prednisolone therapy.
How to cite this article:
Kaul A, Sharma RK, Jaisuresh KS, Agrawal V. Crescentic glomerulonephritis in non-asthmatic Churg-Strauss syndrome.Saudi J Kidney Dis Transpl 2014;25:402-407
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How to cite this URL:
Kaul A, Sharma RK, Jaisuresh KS, Agrawal V. Crescentic glomerulonephritis in non-asthmatic Churg-Strauss syndrome. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2021 Jan 18 ];25:402-407
Available from: https://www.sjkdt.org/text.asp?2014/25/2/402/128580 |
Full Text
Introduction
Non-asthmatic variants of Churg-Strauss syndrome (CSS) are being increasingly reported. [1],[2] Renal involvement is however limited to a few case reports. [3],[4] It is important to identify CSS because of its favorable response to therapy and good long-term prognosis. We present a case of pauci-immune crescentic glomerulonephritis in non-asthmatic CSS and review of the literature on renal involvement in non-asthmatic variants of CSS.
Case Report
A 58-year-old male presented with a 3-week history of low-grade fever, weight loss and progressive distal to proximal weakness, initially involving the upper limbs followed by involvement of the lower limbs. He also reported pins and needles pain in both lower limbs. He denied any history of high blood pressure, asthma, skin lesions, hematuria or oliguria. He denied using any prescriptions, over-the-counter drugs or herbal medications. Physical examination revealed pallor, pulse rate 92/min, blood pressure 150/100 mm Hg, temperature 36.9°C and respiratory rate 15/min.
Cardiac examination was unremarkable. Lungs were clear to auscultation. The abdomen was soft, non-tender and had no palpable hepatosplenomegaly. Neurological examination revealed quadriparesis with signs of sensory and motor polyneuropathy. Electroneurography showed sensorimotor polyneuropathy with signs of axonal damage in the right sural and left common peroneal nerves. His investigations included hemoglobin 9.7 gm/dL, total leukocyte count 9.4 × 1000/μL (4-10 × 1000/ μL) with eosinophils 42%, neutrophils 47%, lymphocytes 10% and monocytes 1%, platelet count 462 cells/mm 3 (150-400 × 1000 cells/ mm 3 ), reticulocyte count 1.2%, serum creatinine 3.8 mg/dL (0.5-1.6 mg/dL), uric acid 7 mg/dL (3.9-8.9 mg/dL), calcium 9.4 mg/dL (9-11 mg/dL), inorganic phosphorus 3.8 mg/dL (2.5-4.5 mg/dL), total bilirubin 0.6 mg/dL (0.1-1.3 mg/dL), direct bilirubin 0.4 mg/dL (0-0.5 mg/dL), total protein 5.9 g/dL (6-8.4 g/dL), albumin 3.8 g/dL (3.5-5.5 g/dL), serum glutamic oxaloacetic transaminase (SGOT) was 16 IU/L (5-40 IU/L), serum glutamic pyruvate transaminase (SGPT) 18 IU/L (5-40 IU/L), alkaline phosphatase 24 U/L (35-150 U/L), lactase dehydrogenase (LDH) 120 IU/L (85-450 IU/L) and creatine kinase-MM 37 μ/L (5-172 μ/L). The C-reactive protein of 7.5 mg/dL (0-0.6 mg/dL) and erythrocyte sedimentation rate of 92 mm/h were elevated. Anti-dsDNA antibody [11.25 IU/mL (normal 0-30 IU/mL)], anti-glomerular basement membrane (anti-GBM) antibody <3 au/mL (0-15 au/mL) and rheumatoid factor titers [7.55 iu/mL, (normal 0-20 IU/mL)] were all within normal limits. Complement levels C3 79.9 mg/dL (normal 60-120 mg/dL) and C4 28.1 mg/ dL (normal 15-30 mg/dL) were also in the normal range. HBsAg and anti-HCV antibody enzyme-linked immunosorbent assays (ELISA) were negative. Computed tomography (CT) of the chest and X-ray of the paranasal sinuses were normal. Urine and blood cultures showed no growth. Pulmonary function tests and echocardiography did not reveal any abnormality. Ultrasound revealed normal-sized kidneys with normal corticomedullary differentiation. Doppler ultrasound of the renal vessels was normal. Urine analysis showed hematuria with 3+ proteinuria. The 24-h proteinuria was 1.8 g in 1900 iriL of urine. There were 0-1 white blood cells per high-power field, 15-20 red blood cells per high-power field and no evidence of casts on microscopic examination of the urine sediment. Perinuclear antineutrophilic cytoplasmic antibody (p-ANCA) titer was raised (247 RU/ML, normal <10 RU/ML) and cytoplasmic antineutrophilic cytoplasmic antibody (c-ANCA) was normal (4.5 RU/ML, normal <10 RU/ML). Anti-myeloperoxidase ELISA was positive and anti-proteinase 3 ELISA was negative.
The diagnosis of p-ANCA-associated vasculitis with rapidly progressive glomerulonephritis was made and ultrasound-guided percutaneous renal biopsy was performed on the fifth day of hospital stay. Light microscopy showed 20 glomeruli, two of which were sclerosed while 12 showed cellular crescents and six showed segmental necrosis and eosinophil infiltration [Figure 1]A and B. The tubules showed focal atropy and the interstitium showed lymphocytic inflammatory infiltrate with several eosinophils. Immunofluorescent micrography revealed absence of specific immunoglobulin or complement (C3, Clq) deposits, consistent with a possible diagnosis of CSS. From Day 5, the patient was treated with intravenous pulse methylprednisolone (500 mg/day, three doses), followed by oral prednisolone 1 mg/kg/day and intravenous cyclophosphamide (750 mg/infusion, first dose). Meanwhile, the patient had progressive deterioration of renal function necessitating dialytic therapy. The patient required alternate day hemodialysis of 4 h duration for maintenance of volume status. Over the next seven days, there was no significant improvement in the neurological or renal status. On Day 12, the patient developed severe lower quadrant abdominal pain and tenderness. As abdomen X-rays showed evidence of perforation, emergency laparotomy was performed. Intraoperative findings included two perforations in the ileum at 3 and 3.5 feet distance from the ileocaecal junction (ICJ) and an ulcer with impending perforation at 4 feet from the ICJ. Segmental ileal resection and endileostomy with mucosal flap were performed. Histopathology of the resected specimen showed evidence transmural inflammation of sub-mucosal and serosal vessels with perivascular infiltrate comprising of lymphomononuclear cells and eosinophils [Figure 1]C-E.{Figure 1}
The patient was continued on maintenance hemodialysis, intravenous methylprednisolone and appropriate supportive care. On Day 13, in view of persistent disease progression, a second dose of intravenous cyclophosphamide was administered (750 mg as infusion) and maintenance dose intravenous steroid was continued. By Day 20, his eosinophil count decreased to 10% (total leukocyte count 11.4 × 1000/μL, 4-10 × 1000/μL), erythrocyte sedimentation rate (ESR) decreased to 23 mm/h and p-ANCA titer was 220 RU/ML. There was significant improvement in hand grip and paresthesias resolved completely. In view of persistent renal failure, immunosuppression was modified to oral cyclophophamide (50 mg/day) with oral prednisolone 10 mg/day from Day 20. On Day 33, the patient was discharged with advice of maintenance hemodialysis, oral cyclophosphamide 50 mg/day, oral prednisolone 10 mg/day, antihypertensives (two drugs) and ileostomy care. Patient's renal function gradually improved and at the end of the 8 th week, he was dialysis independent. After 12 weeks, the patient's eosinophil count was 7%, renal function returned to normal with a subnephrotic proteinuria of 800 mg/day and p-ANCA titer was 145 RU/ML. Cyclophosphamide was tapered and oral prednisolone 10 mg/day was continued. He underwent ileostomy closure and corrective surgery after 24 weeks. At 12 months after the onset of illness, he is relapse free and normotensive, has a serum creatinine of 1.1 mg/dL, 24-h proteinuria 120 mg and normal p-ANCA titers with a regimen of 10 mg/day oral prednisolone.
Discussion
With the presence of sensorimotor polyneuropathy, rapidly progressive glomerulonephritis (RPGN) and p-ANCA positivity, a diagnosis of ANCA-associated vasculitis was made. The differential diagnosis of microscopic polyarteritis, Wegeners granulomatosis (WG) and CSS were considered. Absence of pulmonary involvement and c-ANCA negativity excludes WG. As there was no pulmonary or paranasal sinus involvement, our patient does not satisfy the American College of Rheumatology (ACR) criteria or Lanham criteria for diagnosis of CSS. Microscopic polyarteritis can occasionally show eosinophilia, but presence of extra-vasular eosinophils in renal interstitium and ileal specimen with marked peripheral blood eosinophilia favors CSS. Although vasculitis may precede asthma in CSS, our patient has been observed for 12 months since the onset of vasculitis and he did not develop any evidence of pulmonary involvement thus favoring a diagnosis of non-asthmatic CSS.
Limited forms of CSS are often recognized by eosinophilia and histological findings of skin, lung, intestinal or renal biopsies. Asthma is seen in 98% of CSS patients (classical CSS). Although reports of non-asthmatic CSS are not uncommon, only eight of these patients had renal involvement [Table 1]. [1],[2],[3],[4],[5],[6],[7] Interestingly, pauci-immune necrotizing crescentic glomerulonephritis was the only renal manifestation [Table 1].{Table 1}
Seven of the eight patients had p-ANCA positivity. This indicates a greater prevalence of p-ANCA Myeloperoxidase (MPO) positivity in CSS patients with signs of glomerular involvement. In a study of 116 patients with CSS, Sinico et al [8] found ANCA positivity in 75% of CSS patients with nephropathy as compared with 25.7% in patients without nephropathy.
Another remarkable finding in non-asthmatic CSS is the rapid response to therapy. Steroids with or without cyclophosphamide have obtained renal recovery (complete or partial) in all seven patients. Our patient is interesting due to the rapidly severe multisystem involvement and delayed yet remarkable response to immunosuppressive therapy. Improvement in neurological status and laboratory parameters (eosinophils and ESR) were seen by the second week of therapy and renal functions recovered over a period of 12 weeks. Sinico et al [8] analyzed 31 patients of CSS with renal abnormalities. Eleven patients had necrotising crescentic glomerlonephritis and nine of these 11 patients recovered to a creatinine of 1.3 mg/dL. Only one patient reached end-stage renal failure and no patient had a doubling of serum creatinine level after a mean follow-up of about five years. In comparison, with a mean follow-up of ten months (range 2-17 months), all patients of non-asthmatic CSS in our review have been relapse free. As compared with other ANCA-associated vascilitides, crescentic glomerulonephritis in CSS has good short- and long-term outcomes, and, from our review, it seems to be true even in patients with the limited form (non-asthmatic) of CSS. However, further evidence would be required to generalize this observation.
From the limited experience of case reports, we conclude that pauci-immune necrotizing crescentic glomerulonephritis is the most frequent renal lesion in non-asthmatic CSS, and more than 90% patients show p-ANCA positivity. Renal recovery and prognosis of crescentic glomerulonephritis in patients of non-asthmatic CSS and classical CSS are comparable.
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